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Cell therapy for cardiac repair—lessons from clinical trials

Nature Reviews Cardiology volume 11, pages 232–246 (2014)Cite this article

Subjects

Key Points

  • First-generation stem cells are comprised of unselected cell mixtures exemplified by unfractionated bone-marrow-derived mononuclear stem cells

  • Initial stem-cell trials have established safety and feasibility, but show limited efficacy in the context of cardiovascular disease

  • The main hurdles to achieving benefit from stem-cell therapy include poorly defined cell populations, quality control in cell processing, and limited efficiency in cell delivery

  • To improve the regenerative effect, investigators have focused on purified cell populations to eliminate nonregenerative cells

  • Next-generation cell therapy ushers a new era in regenerative medicine by targeting organ or disease before implantation

  • The interplay between the diseased heart and regenerative biotherapeutics is critical in achieving repair

Abstract

The global impetus to identify curative therapies has been fuelled by the unmet needs of patients in the context of a growing heart failure pandemic. To date, regeneration trials in patients with cardiovascular disease have used stem-cell-based therapy in the period immediately after myocardial injury, in an attempt to halt progression towards ischaemic cardiomyopathy, or in the setting of congestive heart failure, to target the disease process and prevent organ decompensation. Worldwide, several thousand patients have now been treated using autologous cell-based therapy; the safety and feasibility of this approach has been established, pitfalls have been identified, and optimization procedures envisioned. Furthermore, the initiation of phase III trials to further validate the therapeutic value of cell-based regenerative medicine and address the barriers to successful clinical implementation has led to resurgence in the enthusiasm for such treatments among patients and health-care providers. In particular, poor definition of cell types used, diversity in cell-handling procedures, and functional variability intrinsic to autologously-derived cells have been identified as the main factors limiting adoption of cell-based therapies. In this Review, we summarize the experience obtained from trials of 'first-generation' cell-based therapy, and emphasize the advances in the purification and lineage specification of stem cells that have enabled the development of 'next-generation' stem-cell-based therapies targeting cardiovascular disease.

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Figure 1: Mechanistic basis for regeneration, and the fate of progenitors after transplantation into the myocardium.
Figure 2: Approaches to isolation and preparation of stem cells for regenerative cardiovascular medicine.

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  1. Center for Regenerative Medicine and Division of Cardiovascular Diseases, Mayo Clinic, 200 1st Street SW, Rochester, 55905, MN, USA

    Atta Behfar, Ruben Crespo-Diaz, Andre Terzic & Bernard J. Gersh

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  1. Atta Behfar
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  2. Ruben Crespo-Diaz
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All authors researched data for the article, substantially contributed to discussion of content, wrote, and reviewed and edited the manuscript before submission.

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Behfar, A., Crespo-Diaz, R., Terzic, A. et al. Cell therapy for cardiac repair—lessons from clinical trials. Nat Rev Cardiol 11, 232–246 (2014). https://doi.org/10.1038/nrcardio.2014.9

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